PMID: 3758307Aug 1, 1986Paper

Effects of administration of metabolic inducers and inhibitors on pulmonary toxicity and covalent binding by 1,1-dichloroethylene in CD-1 mice

Experimental and Molecular Pathology
P G ForkertW J Racz

Abstract

The administration of 1,1-dichloroethylene (1,1-DCE, 125 mg/kg ip) to CD-1 mice caused bronchiolar necrosis, which was accompanied by substantial covalent binding of radiolabeled compound and/or metabolite to lung. Lung injury and covalent binding were not modified by phenobarbital pretreatment. However, 3-methylcholanthrene provided a protective influence but failed to alter covalent binding to lung macromolecules. Prior administration with the metabolic inhibitors, piperonyl butoxide and SKF 525-A, produced differential effects. While piperonyl butoxide exacerbated bronchiolar injury by 1,1-DCE, covalent binding remained unaltered. In contrast, SKF 525-A protected from lung damage and significantly decreased covalent binding. Hepatic necrosis was relatively mild, and was not observed in all animals treated with 1,1-DCE. Although the hepatic lesion was not modified by phenobarbital, liver injury was slightly diminished by 3-methylcholanthrene. The inducers, piperonyl butoxide and SKF 525-A, enhanced liver necrosis, with the latter eliciting more severe effects than the former agent. Covalent binding to liver tissues was not significantly changed by pretreatment with either inducers or inhibitors. These results indicate that la...Continue Reading

References

Feb 1, 1986·Canadian Journal of Physiology and Pharmacology·P G ForkertK M Troughton
Aug 1, 1985·Toxicology·P G ForkertE S Reynolds
Nov 1, 1985·Canadian Journal of Physiology and Pharmacology·P G Forkert
Apr 1, 1973·The American Review of Respiratory Disease·W D ReidG Krishna
Mar 28, 1980·Science·C J Serabjit-SinghC G Plopper
Feb 1, 1982·Experimental Lung Research·P G Forkert, E S Reynolds
Nov 1, 1981·Toxicology and Applied Pharmacology·K A GriffinR B Franklin
Oct 1, 1980·Chemico-biological Interactions·J D Sun, J G Dent
Mar 12, 1965·Annals of the New York Academy of Sciences·H REMMER, H J MERKER

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Citations

Apr 14, 1995·Chemico-biological Interactions·T F DowsleyJ L Bolton
Mar 29, 2001·Drug Metabolism Reviews·P G Forkert
Jun 25, 2020·BMC Pulmonary Medicine·Shanjana AwasthiStanley Kosanke

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